Acquired Immunodeficiency Syndrome (AIDS)

History u 1950s: Blood samples from Africa have HIV antibodies. u 1976: First known AIDS patient died. u 1980: First human retrovirus isolated (HTLV-1). u 1981: First reports of “Acquired Immuno- deficiency Syndrome” in Los Angeles. u 1983: Virus first isolated in France (LAV). u 1984: Virus isolated in the U.S. (called HTLV-III and AIDS-Related Virus, ARV). u 1985: Development and implementation of antibody test to screen blood donors.

Acquired Immunodeficiency Syndrome (AIDS) History (Continued) History (Continued) u 1986: Consensus name Human Immunodeficiency Virus (HIV-1). Related virus (HIV-2) identified. u 1992: AIDS becomes the leading cause of death among adults ages in the U.S. u 1997: Mortality rates of AIDS starts to decline due to the introduction of new drug cocktails. u 2001: World Health Organization predicts up to 40 million infected individuals. More than 22 million have already died.

AIDS: A Leading Cause of Death Among People Aged years in U.S. Deaths per 100,000 people aged years

People Living with HIV/AIDS by End of 2001 North America 950,000 Latin America 1.5 million Western Europe 560,000 East Europe & Central Asia 1’000,000 Sub-Saharan Africa 28.5 million North Africa & Middle East 500,000 Australia & New Zealand 15,000 South/South East Asia 5.6 million East Asia & Pacific 1’000,000 Total: 40 million people Caribbean 420,000

Structure of the Human Immunodeficiency Virus HIV is a Retrovirus

Life Cycle of HIV 1. Attachment: Virus binds to surface molecule (CD4) of T helper cells and macrophages. F Coreceptors: Required for HIV infection. F CXCR4 and CCR5 mutants are resistant to infection. 2. Fusion: Viral envelope fuses with cell membrane, releasing contents into the cell.

HIV Life Cycle: Attachment Requires CD4 Receptor plus a Coreceptor

Life Cycle of HIV 3. Reverse Transcription: Viral RNA is converted into DNA by unique enzyme reverse transcriptase. Reverse transcriptase RNA > DNA Reverse transcriptase is the target of several HIV drugs: AZT, ddI, and ddC.

HIV Life Cycle: Reverse Transcriptase Converts RNA into DNA

A must see to review the medications for HIV Wait for the video to load

Life Cycle of HIV 4. Integration: Viral DNA is inserted into host cell chromosome by unique enzyme integrase. Integrated viral DNA may remain latent for years and is called a provirus. 5. Replication: Viral DNA is transcribed and RNA is translated, making viral proteins. Viral genome is replicated. 6. Assembly: New viruses are made. 7. Release: New viruses bud through the cell membrane. spx?itemnum=11388

HIV Life Cycle: Latent versus Active Infection

HIV Life Cycle: Latent versus Active Infection in Macrophages

AIDS Associated Disease Categories 1. Gastrointestinal: Cause most of illness and death of late AIDS. Symptoms: u Diarrhea u Wasting (extreme weight loss) u Abdominal pain u Infections of the mouth and esophagus. Pathogens: Candida albicans, cytomegalovirus, Microsporidia, and Cryptosporidia.

African AIDS patient with slim disease Source: Tropical Medicine and Parasitiology, 1997

Opportunistic Oral Yeast Infection by Candida albicans in an AIDS Patient Source: Atlas of Clinical Oral Pathology, 1999

AIDS Associated Disease Categories 2. Respiratory: 70% of AIDS patients develop serious respiratory problems. Partial list of respiratory problems associated with AIDS: F Bronchitis F Pneumonia F Tuberculosis F Lung cancer F Sinusitis F Pneumonitis

Chest X-Ray of AIDS Patient with Tuberculosis

AIDS Associated Disease Categories 3. Neurological: Opportunistic diseases and tumors of central nervous system. Symptoms many include: Headaches, peripheral nerve problems, and AIDS dementia complex (Memory loss, motor problems, difficulty concentration, and paralysis).

AIDS Associated Disease Categories 4. Skin Disorders: 90% of AIDS patients develop skin or mucous membrane disorders. F Kaposi’s sarcoma 1/3 male AIDS patients develop KS1/3 male AIDS patients develop KS Most common type of cancer in AIDS patientsMost common type of cancer in AIDS patients F Herpes zoster (shingles) F Herpes simplex F Thrush F Invasive cervical carcinoma 5. Eye Infections: 50-75% patients develop eye conditions. F CMV retinitis F Conjunctivitis F Dry eye syndrome

Extensive tumor lesions of Kaposis’s sarcoma in AIDS patient. Source: AIDS, 1997

Chronic Herpes Simplex infection with lesions on tongue and lips. Source: Atlas of Clinical Oral Pathology, 1999.

Non-Hodgkin’s Lymphoma & ascites in AIDS patient Source: Tropical Medicine and Parasitiology, 1997

Drugs Against HIV u Reverse Transcriptase Inhibitors: Competitive enzyme inhibitors. Example: AZT, ddI, ddC. u Protease Inhibitors: Inhibit the viral proteases. Prevent viral maturation. u Problem with individual drug treatments: Resistance. u Drug Cocktails: A combination of: F One or two reverse transcriptase inhibitors F One or two protease inhibitors. u Drug cocktails have been very effective in suppressing HIV replication and prolonging the life of HIV infected individuals, but long term effectiveness is not clear.

Stages of HIV Infection

Antibody Levels, T Cell Counts, and HIV Concentration After Infection

Transmission of AIDS (Worldwide) 1. Sexual contact with infected individual: All forms of sexual intercourse (homosexual and heterosexual). 75% of transmission. 2. Sharing of unsterilized needles by intravenous drug users and unsafe medical practices: 5- 10% of transmission. 3. Transfusions and Blood Products: Hemophiliac population was decimated in 1980s. Risk is low today. 3-5% of transmission. 4. Mother to Infant (Perinatal): 25% of children become infected in utero, during delivery, or by breast-feeding (with AZT only 3%). 5-10% of transmission.

HIV Transmission in United States and Rest of the World

www. Wepapers.com/papers/76496/HIV_teasting.ppt www. Wepapers.com/papers/76496/HIV_teasting.ppt click on the HIV Testing.ppt in the upper left Conner and walk through the testing slides